Microfluidic devices or substrates typically consist of two or more microchannels or capillaries that can range in size from about 5-100 μm wide and 5-100 μm deep etched or molded in a substrate that can be silicon, plastic, quartz, glass, or plastic. Microfluidic substrates may be fabricated using photolithographic techniques similar to those used in the semiconductor industry, and the resulting devices can be used to perform a variety of sophisticated chemical and biological analytical techniques. Microfluidic analytical technology has a number of advantages, including the ability to use very small sample sizes, typically on the order of nanoliters. The substrates may be produced at a relatively low cost, and can be formatted to perform numerous specific analytical operations, including mixing, dispensing, valving, reactions, and detections.
Another recently developed class of sample-receiving microfluidic substrates includes substrates having a capillary interface that allows compounds to be brought onto the test substrate from an external source, and which can be advantageously used in a number of assay formats for high-throughput screening applications. These assay formats include fluorogenic assays, fluorescence polarization assays, non-fluorogenic mobility shift assays, dose response assays, and calcium flux cell-based assays.
Other applications for microfluidic devices include diagnostics involving biomolecules and other analytical techniques such as micro total analysis systems. Such devices, often referred to in the art as “microchips,” also may be fabricated from plastic, with the channels being etched, machined or injection molded into individual substrates. Multiple substrates may be suitably arranged and laminated to construct a microchip of desired function and geometry. In all cases, the channels used to carry out the analyses typically are of capillary scale dimension.
To fully exploit the technological advances offered by the use of microfluidic devices and to maintain the degree of sensitivity for analytical techniques when processing small volumes, e.g., microliters or less, connectors which introduce and/or withdraw fluids, i.e., liquids and gases, from the device, as well as interconnect microfluidic devices, are crucial components in the use and performance of the microfluidic device. For example, chromatographic applications require an injection port that can introduce a sample into a flow stream. The varied uses of these microfluidic devices require connectors that are both versatile and resilient. The physical stresses placed on these connectors can be demanding. Not only must the connectors be inert to reactive substances that are injected into the microchannels, such as organic solvents, but also they must remain leak free when exposed to pressures that can reach as high as 10,000 psi. Moreover, these connectors must be able to act as an interface for connecting microscale devices such as injectors and fluid reservoirs to microscale capillary tubes. However, because of the extremely small tolerances involved, this has been difficult to achieve. Typically, capillary tubes have outer diameters on the order of 150 to 365 μm and nominal internal diameters of from 50 to 75 μm or less with tolerances as small as a few microns, yet these capillary tubes must be accurately aligned.
A common technique used in the past involves bonding a length of tubing to a port on the microfluidic device with epoxy or other suitable adhesive. Adhesive bonding is unsuitable for many chemical analysis applications because the solvents used attack the adhesive which can lead to channel clogging, detachment of the tubing, and/or contamination of the sample and/or reagents in or delivered to the device. Furthermore, adhesive bonding results in a permanent attachment of the tubing to the microfluidic device which makes it difficult to change components, i.e., either the microfluidic device or the tubing, if necessary. Thus assembly, repair and maintenance of such devices become labor and time intensive, a particularly undesirable feature when the microfluidic device is used for high throughput screening of samples such as in drug discovery.
To avoid problems associated with adhesive bonding, other techniques have been proposed, e.g., press fitting the tubing into a port on the microfluidic device. However, such a connection typically is unsuitable for high-pressure applications such as HPLC. Additionally, pressing the tubing into a port creates high stress loads on the microfluidic device which could lead to fractures of the channels and/or device.
Other methods involved introducing liquids into an open port on the microfluidic device with the use of an external delivery system such as a pipette. However, this technique also is undesirable due to the possibility of leaks and spills which may lead to contamination. In addition, the fluid is delivered discretely rather than continuously. Moreover, the use of open pipetting techniques does not permit the use of elevated pressure for fluid delivery such as delivered by a pump, thereby further restricting the applicability of the microfluidic device.
Microfluidic devices generally comprise an array of micron-sized wells or reservoirs and interconnecting channels disposed on a substrate. The wells are connected to distribution means for dispensing fluids to and collecting fluids from the array. Connection to the wells is typically by means of a micropipette end. While this serves for benign addition of fluids, this means of fluid addition cannot be used for those applications where the access ports are exposed to a pressure differential or where it is desired to connect capillary tubes to fluid wells.
Typically, in microscale devices the microchannels are terminated by ports or wells that provide access to the microchannels. Materials are added to the microchannels through these ports or wells. Access to the ports is typically by means of a micropipette end. While this serves for benign addition fluids it cannot be used for those applications where the access ports are exposed to a pressure differential or adverse environments.
Therefore, a need exists for an improved microfluidic connector which is useful with all types of microfluidic devices and which provides an effective, high pressure connector with low fluid dead volume seal. In general, the connector should be able to connect a first set of capillaries to a second set of capillaries. The first set can be external capillaries whereas the second set can be from a microfluidic device.